Projects per year
Abstract
11β-Hydroxysteroid dehydrogenase-1 (11β-HSD1) plays a key role in glucocorticoid receptor (GR) activation. Besides, it metabolizes some oxysterols and bile acids (BAs). The GR regulates BA homeostasis; however, the impact of impaired 11β-HSD1 activity remained unknown. We profiled plasma and liver BAs in liver-specific and global 11β-HSD1-deficient mice. 11β-HSD1-deficiency resulted in elevated circulating unconjugated BAs, an effect more pronounced in global than liver-specific knockout mice. Gene expression analyses revealed decreased expression of the BA-CoA ligase Fatp5, suggesting impaired BA amidation. Reduced organic anion-transporting polypeptide-1A1 (Oatp1a1) and enhanced organic solute-transporter-β (Ostb) mRNA expression were observed in livers from global 11β-HSD1-deficient mice. The impact of 11β-HSD1-deficiency on BA homeostasis seems to be GR-independent because intrahepatic corticosterone and GR target gene expression were not substantially decreased in livers from global knockout mice. Moreover, Fatp5 expression in livers from hepatocyte-specific GR knockout mice was unchanged. The results revealed a role for 11β-HSD1 in BA homeostasis.
Original language | English |
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Pages (from-to) | 554-64 |
Number of pages | 11 |
Journal | Molecular metabolism |
Volume | 3 |
Issue number | 5 |
Early online date | 2 May 2014 |
DOIs | |
Publication status | Published - Aug 2014 |
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Dive into the research topics of '11β-Hydroxysteroid dehydrogenase-1 is involved in bile acid homeostasis by modulating fatty acid transport protein-5 in the liver of mice'. Together they form a unique fingerprint.Projects
- 2 Finished
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Centre for Musculoskeletal Ageing Research (linked to 18289 & 19482)
Lord, J., Buckley, C., Duda, J., Dunn, W., Miall, C. & Greig, C.
1/08/12 → 31/07/17
Project: Research Councils
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Investigating Hexose-6-Phosphate Dehydrogenase in the Control of Skeletal Muscle Function and Carbohydrate Metabolism
Lavery, G.
Biotechnology & Biological Sciences Research Council
1/09/09 → 31/08/14
Project: Research Councils